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Thread: Magnesium and zinc, MXE and NDMA antagonists for depression?

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    Magnesium and zinc, MXE and NDMA antagonists for depression? 
    #1
    Bluelighter DexterMeth's Avatar
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    Someone just pointed out to me in OD forum that magnesium and zinc are both NDMA antagonists. If this is so, could they possibly be an aid in combatting depression, similar to how MXE and ketamine work for this?

    Also, does this mean that supplimenting with both magnesium and zinc, via vitamins, would raise one's tolerance to psychoactives such as the two mentioned?

    If the answer to this is already relatively known and strait forward, please supply links.

    Thank you
     

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    #2
    Ketamine and presumably MXE aren't something I would really look at for depression despite all the recent studies that have come out. There is a lot of evidence pointing to negatives for sustained usage, especially in abuse settings. There's also the fact that some people that browse this forum might take this info as an excuse to run out and k-hole themselves, so right now I'll say that this is a very bad idea until some sort of peer reviewed study comes out regarding an appropriate dosing regime (yes I know researchers have posted short term human trials). So, there might be some novel antidepressants that come out in the next decade that use this mechanism of action if it all pans out.

    http://www.nature.com/clpt/journal/v...t2011244a.html Review of the current relationship between ketamine and depression.

    Summed up: some types NMDA antagonism are associated with improvements in depression, but ketamine is a dirty as hell drug so its surprising efficacy could just as easily be a result of its AMPA potentiating actions or a combination of various mechanisms. In fact in most animal studies NBQX (a AMPA antagonist) blocked its antidepressant effects. Zinc and magnesium do block NMDAR in addition to more than a handful of other actions in the body, but I'll say short of cases of deficiency, megadoses won't be of much help for tolerance or depression though a multivitamin a day never hurts.

    But, rather than deal with the legal issues associated with ketamine. Why not drink some cough syurp!?!? But, seriously DXM if not OTC and unpatentable would probably be pushed harder than anything else as a new antidepressant. Its safe, well characterized, has multiple relevant mechanisms of action, and on paper looks like the next best thing aside from getting off the couch and eating right you could do for depression.
    http://www.ncbi.nlm.nih.gov/pubmed/22401777
    http://www.ncbi.nlm.nih.gov/pubmed/22339643
    http://www.sciencedirect.com/science...06987711002246
    Last edited by Epsilon Alpha; 20-04-2012 at 05:06.
     

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    #3
    Bluelighter DexterMeth's Avatar
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    Quote Originally Posted by Epsilon Alpha View Post
    Ketamine and presumably MXE aren't something I would really look at for depression despite all the recent studies that have come out. There is a lot of evidence pointing to negatives for sustained usage, especially in abuse settings. There's also the fact that some people that browse this forum might take this info as an excuse to run out and k-hole themselves, so right now I'll say that this is a very bad idea until some sort of peer reviewed study comes out regarding an appropriate dosing regime (yes I know researchers some have posted short term human trials). So, there might be some novel antidepressants that come out in the next decade that use this mechanism of action if it all pans out.

    http://www.nature.com/clpt/journal/v...t2011244a.html Review of the current relationship between ketamine and depression.

    Summed up: some types NMDA antagonism are associated with improvements in depression, but ketamine is a dirty as hell drug so its surprising efficacy could just as easily be a result of its AMPA potentiating actions or a combination of various mechanisms. In fact in most animal studies NBQX (a AMPA antagonist) blocked its antidepressant effects. Zinc and magnesium do block NMDAR in addition to more than a handful of other actions in the body, but I'll say short of cases of deficiency, megadoses won't be of much help for tolerance or depression though a multivitamin a day never hurts.

    But, rather than deal with the legal issues associated with ketamine. Why not drink some cough syurp!?!? But, seriously DXM if not OTC and unpatentable would probably be pushed harder than anything else as a new antidepressant. Its safe, well characterized, has multiple relevant mechanisms of action, and on paper looks like the next best thing aside from getting off the couch and eating right you could do for depression.
    http://www.ncbi.nlm.nih.gov/pubmed/22401777
    http://www.ncbi.nlm.nih.gov/pubmed/22339643
    http://www.sciencedirect.com/science...06987711002246
    Thanks for the links and input. I agree with your general sentiment of not using ketamine (or MXE for that matter) to combat depression (long-term), as well as the anti-harm reduction message that using K for this might send. I still think, knowing a lot more about the psychophmacology, that using it (or MXE) for single use break through out of depression, prove to be very beneficial. The same could be said for a lot of psychoactives, yes, and especially psychedelics; but this is where NMDA potentiation comes into play, if I am understanding this correctly.

    ---
    I'll have to read up on AMPA. I don't even know what that system(?) is.

    ---
    Exercise and proper diet are indeed integral, but you left out sleep.

    ---
    I'll come back to this thread after reading through those links and learning about AMPA, if you even leave this open.


    edit: Actually I see your harm reduction statement even more so now, because this is the ADD forum, not the bible..well arguably. Even fastandbublous has been wrong, and more than once.
     

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    #4
    If your depression is light/transient, I find aniracetam immediatly stops negative thoughts and sets me straight. I mostly mention as it is an ampa modulator, which fits with the mechanism you described for ketamine. I've had multiple people say the same about it(after convincing them to try it/buy some).

    Plus taking aniracetam is extremely safe(as far as I know, and I regularly look for new studies on it(not much luck lol) and look for any I missed). I've taken up to ~10 grams once and usually around 1-2 grams when I do take it(and I've used before for about 6mo, greatly increased my well being, but I've written about it on that aspect too many times). Nothing ever negative, never makes the depression worse or any after effects except brighter colors and crisper vision(and some type of enhanced 3d perception.. very cool for me).

    I'm no doctor and I'll admit it's self medication, however I never felt that "self medication" was an inherently bad term like its oft referred to everywhere, maybe not so much here lol(I mean in many instances it is bad though because it is just an escape and there is no doctor to control the downward spiral that results). However aniracetam I feel safe saying that I self medicate with and have never run into anything like addiction to it or the NEED to take it, etc..
     

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    #5
    I'll agree that dxm can be great for depression, has some very positive effects. I liked saying people would run out and khole themselves, and I would love to do that. I always found ketamine to be very enjoyable for me, and not dirty as you say, however, to each their own.
     

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    #6
    Quote Originally Posted by LeLouche View Post
    I'll agree that dxm can be great for depression, has some very positive effects. I liked saying people would run out and khole themselves, and I would love to do that. I always found ketamine to be very enjoyable for me, and not dirty as you say, however, to each their own.
    I'm referring to the fact that it binds to a ridiculous number of targets, as does DXM. It means that NMDA inhibition may not be its primary MOA in depression, as it also acts on (off the top of my head) voltage gated sodium channels, DRI, sigma ligand, MOR, iNOS inhibitor, calcium channel blocker, and it had some weird actions on the genomic level too.
     

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    #7
    Pretty sure he means dirty pharmacologically, meaning that it hits a ton of receptors/other effects rather than being selective.

    think alcohol(pretty much everything), ibogaine(pretty much everything), or lsd(binds to way more serotonin and dopamine receptors than other psyches, plus others) versus benzos(gaba-a, some other effects), psilocin(mostly5ht2a, 2c, 1a, and possibly some dopamine receptors) etc.

    edit: lol, useless post now
     

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    #8
    Bluelighter DexterMeth's Avatar
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    Quote Originally Posted by golden1 View Post
    If your depression is light/transient, I find aniracetam immediatly stops negative thoughts and sets me straight. I mostly mention as it is an ampa modulator, which fits with the mechanism you described for ketamine. I've had multiple people say the same about it(after convincing them to try it/buy some).

    Plus taking aniracetam is extremely safe(as far as I know, and I regularly look for new studies on it(not much luck lol) and look for any I missed). I've taken up to ~10 grams once and usually around 1-2 grams when I do take it(and I've used before for about 6mo, greatly increased my well being, but I've written about it on that aspect too many times). Nothing ever negative, never makes the depression worse or any after effects except brighter colors and crisper vision(and some type of enhanced 3d perception.. very cool for me).

    I'm no doctor and I'll admit it's self medication, however I never felt that "self medication" was an inherently bad term like its oft referred to everywhere, maybe not so much here lol(I mean in many instances it is bad though because it is just an escape and there is no doctor to control the downward spiral that results). However aniracetam I feel safe saying that I self medicate with and have never run into anything like addiction to it or the NEED to take it, etc..
    Getting off-topic, but have you tried piracetam?

    I just realized that the Keppra I take is a racetam. Wtf? I already take piracetam @1 gram 4x a day.
     

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    #9
    Quote Originally Posted by DexterMeth View Post
    Getting off-topic, but have you tried piracetam?

    I just realized that the Keppra I take is a racetam. Wtf? I already take piracetam @1 gram 4x a day.
    yes piracetam is good too, but if I had to choose one(I've taken pir,ani,oxi,pram,nefi) it would be aniracetam for sure, then piracetam.. the others weren't that useful for anything(pramiracetam for endurance when studying but I didn't like the subjective feel at all, oxi was alright but could induce depression, and nefi was really neat meditative like however it felt toxic to the rest of my body).
    if you want comparison it's rather hard, but piracetam is decently more subtle while still obvious when aniracetam is very obvious for me(it has a feeling to it kind of like a slight weed/psy/benzo feeling..but obv much less so than any of the 3 even on their own). They do very similar things, but aniracetam seems to be more potent at them and have better stress reducing effects and more of a laid back focus compared to piracetam's alert focus.(thats best I can do, esp considering they vary so much person to person)

    and yeah keppra is a racetam, but it seems quite different in effect and side effects(I've never tried since it's not nootropic, but anti-seizure).
     

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    #10
    http://www.bloomberg.com/news/2010-1...ng-crying.html
    Well shave my balls and call me Sandy... They actually got a quinidine-DXM combo FDA approved as a prescription drug!
    And, weirdly enough the stuff just screams promise in bipolar/borderline personality. I really want to see some more studies on this
    http://www.ncbi.nlm.nih.gov/pubmed/22326841
     

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    #11
    Bluelighter DexterMeth's Avatar
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    ^wow. I'm checking that out now. Probably better than ketamine/MXE, and something a lot more reasonable to use daily, no?
    -edit: Neudexta sounds very promising. I am going to get my doctor to prescribe it to me and see how it goes.

    It's DXM and quinidine.
    Quote Originally Posted by golden1 View Post
    yes piracetam is good too, but if I had to choose one(I've taken pir,ani,oxi,pram,nefi) it would be aniracetam for sure, then piracetam.. the others weren't that useful for anything(pramiracetam for endurance when studying but I didn't like the subjective feel at all, oxi was alright but could induce depression, and nefi was really neat meditative like however it felt toxic to the rest of my body).
    if you want comparison it's rather hard, but piracetam is decently more subtle while still obvious when aniracetam is very obvious for me(it has a feeling to it kind of like a slight weed/psy/benzo feeling..but obv much less so than any of the 3 even on their own). They do very similar things, but aniracetam seems to be more potent at them and have better stress reducing effects and more of a laid back focus compared to piracetam's alert focus.(thats best I can do, esp considering they vary so much person to person)

    and yeah keppra is a racetam, but it seems quite different in effect and side effects(I've never tried since it's not nootropic, but anti-seizure).
    I am going to have to try aniracetam next. That will probably become my daily one to use. Nefi sounds promising for when I have nothing to do.

    Should I be using choline with all racetams? Speaking of choline, would that interfere with my Keppra?
    Last edited by DexterMeth; 13-05-2012 at 05:53.
     

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    #12
    Yes, choline is pretty essential for racetam use..forgot why, but theres plenty of info about it..something to do with the racetams depleting acetylcholine..I notice a huge difference if I take piracetam alone, or if i add choline bitartrate. Less fog, more acuity and sharpness. Don't know if it will interfere with Keppra . I would venture a NO but might wanna do some more research. Especially considering its for seizure control and blood levels should be monitored with that drug.. idk if choline will alter the pharmacodynamics at all..
    Thats pretty cool they r have a dxm med approved.
     

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    #13
    Bluelighter DexterMeth's Avatar
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    I was reading more about Neudextra today. I take it it's very expensive, even though DXM and quinidine can be obtained seperately, in bulk, for 1/100th of price of an RX for a year of Neudextra, for a life-time supply of each.

    I actually did not even take Keppra (levetiracetam) into account with taking choline. Thanks. I'll report back in a week or so about the effects.
     

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    #14
    I'm taking Magnesium Oxide as an NMDA receptor antagonist. I stumbled onto it by accident looking for something to help with sleep (formerly a heavy user of diphenhydramine). Much to my surprise, it significantly reduced my chronic tremors. I'm now taking 6 x 500mg daily and have been for a couple weeks with no side effects at all.

    I'm not sure what effect Magnesium would have on depression. I too am looking into zinc (how I found this post) as a possibly synergy for the magnesium.

    If you do look into this direction, be aware that bioavailability of magnesium varies greatly. Magnesium Oxide is cheap and easy to get, but not very high in availability. I want to try Magnesium Citrate which I've heard is better. There are several others.

    Anyone have suggestions on the form of zinc for oral supplementation? My vendor carries Oxide, Sulfate and Picolinate.
     

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    #15
    Quote Originally Posted by Epsilon Alpha View Post
    http://www.bloomberg.com/news/2010-1...ng-crying.html
    Well shave my balls and call me Sandy... They actually got a quinidine-DXM combo FDA approved as a prescription drug!
    And, weirdly enough the stuff just screams promise in bipolar/borderline personality. I really want to see some more studies on this
    http://www.ncbi.nlm.nih.gov/pubmed/22326841
    Great find, Sandy!

    Both with fairly long histories of positive safety profiles.

    Quote Originally Posted by DexterMeth View Post
    Should I be using choline with all racetams?
    This is frequently debated. Most recently, the more informed people I've spoken with (I don't know much about the racetams) have suggested starting without choline. The initial headache is presumed to be due to an improper ratio on either side. Therefore, titrating up is faster and more clearly understood compared to shooting for the 1:2 or 1:1 ratio people recommend and tinkering back and forth. I suppose you'd want to consider your diet as well.
     

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